1.
Acquired (adaptive) immunity
⚫ The resistance that human acquires during life is
known as acquired immunity.
⚫ Also known as adaptive immunity.
⚫ Acquired immunity is caused by a special
immune system that forms antibodies and/or
activated lymphocytes that attack and destroy
the specific invading organism or toxin.

2.
Adaptive immunity: Basic type
Humoral immune response (HIR) or B-cell
immunity
⚫ B-lymphocytes
⚫ mediated by antibodies
⚫ eliminate extra-cellular microbes and their toxins
Cell-mediated immune response (CMIR) or T-cell
immunity
⚫ T-lymphocytes
⚫ eliminate intracellular microbes that survive
within phagocytes or other infected cells

3.
Antigens
⚫ an antigen is a molecule capable of inducing
an immune response (to produce an antibody) in
the host organism.
⚫ In general, these are proteins or large
polysaccharides,
⚫ antigens (antibody generations).
⚫ For a substance to be antigenic, it usually must
have a high molecular weight of 8000 or greater.

4.
B-Lymphocyte
⚫ B lymphocytes are formed in the liver during mid fetal
life and in the bone marrow during late fetal life and
after birth.
⚫ B lymphocyte was first discovered in birds, which have
a special pre-processing organ called the bursa of
Fabricius. For this reason, these lymphocytes are called
“B” lymphocytes to designate the role of the bursa

5.
⚫ immature B cells migrate from the bone marrow in
the lymphoid organs such as the spleen and
lymph nodes which receive a constant supply of
antigen through circulating lymph.
⚫ The B lymphocytes actively secrete antibodies
that are the reactive agents and are capable of
combining with and destroying the antigenic
substance.
⚫ B lymphocytes have greater diversity than the T
lymphocytes, thus forming many millions of types
of B-lymphocyte antibodies

6.
B cell development
⚫ B cells undergo two types of selection while
developing in the bone marrow to ensure proper
development, both involving B cell receptors
(BCR) on the surface of the cell.
⚫ Positive selection If the B cell receptors do not
bind to their ligand, B cells do not receive the
proper signals and cease to develop.
⚫ Negative selection occurs through the binding of
self-antigen with the BCR. If the BCR bind strongly
to self-antigen, then the B cell undergoes clonal
deletion or clonal anergy.
⚫ This negative selection process leads to a state of
central tolerance, in which the mature B cells do
not bind self antigens present in the bone marrow

7.
⚫ B cell activation occurs in the secondary
lymphoid organs (SLOs), such as the spleen and
lymph nodes.
⚫ After B cells mature in the bone marrow, they
migrate through the blood to SLOs, which receive
a constant supply of antigen through circulating
lymph.
⚫ At the SLO, B cell activation begins when the B
cell binds to an antigen.

8.
T and B lymphocyte formation

9.
Humoral Immunity And The Antibodies
Formation of antibody:
⚫ Upon entry of a foreign antigen, macrophages in
lymphoid tissue phagocytize the antigen and then
present it to adjacent B lymphocytes.
⚫ The B lymphocytes specific for the antigen
immediately enlarge and take on the appearance
of lymphoblasts.
⚫ Some of the lymphoblasts further differentiate to
form plasmablasts.

10.
⚫ The plasmablasts then divide slowly over to form
plasma cell.
⚫ plasma cell then produces gamma globulin
antibodies at an extremely rapid rate—about
2000 molecules per second for each plasma cell.
⚫ This process continues for several days or weeks
until finally exhaustion and death of the plasma
cells occur.

11.
⚫ Plasma cells can be generally divided into two
distinct categories based on their lifespan:
 (a) short-lived plasma cells/plasmablasts (proliferating
cells with a life span of 3–5 days) and
 (b) long-lived plasma cells (non-proliferating cells with
a life span of several months to lifetime).
⚫ The short-lived plasma cells provide rapid
protection but undergo apoptosis after a few
days of intense antibody secretion.
⚫ However, the long-lived plasma cells reside in
tissues such as the bone marrow and gut-
associated lymphoid tissue and can continue
producing antibodies for many years, providing
lifelong immunity against infectious diseases
such as measles and smallpox

12.
B cell activation and Function

13.
Memory cells formation:
⚫ Few of the lymphoblasts formed by do not go on to
form plasma cells but instead form moderate
numbers of new B lymphocytes similar to those of the
original clone.
⚫ The B-cell population of the specifically activated
clone becomes greatly enhanced.
⚫ These lymphocytes are called memory cells.
⚫ Subsequent exposure to the same antigen will cause
a much more rapid and much more potent antibody
response this second time

14.
Antibodies
⚫ Antibodies are gamma globulins called
immunoglobulins (Ig) that have molecular weights
between 160,000 and 970,000 Dalton and
constitute about 20 percent of all the plasma
proteins.
⚫ All the immunoglobulins are composed of
combinations of light and heavy polypeptide
chains.
⚫ Most are a combination of two light and two
heavy chains

15.
Schematic structure of an antibody: two heavy chains
(blue, yellow) and the two light chains (green, pink).
The antigen binding site is circled.

16.
⚫ The variable portion is different for each specific
antibody, and it is this portion that attaches
specifically to a particular type of antigen.
⚫ A combination of noncovalent and covalent bonds
(disulfide) holds the light and heavy chains
together.
⚫ Antibodies have more than one antigen combining
site
⚫ Some bivalent Ab molecules can combine to form
multimeric Abs that have upto 10 combining sites

17.
Classes of Antibody
⚫ There are five general classes of antibodies,
respectively named
 IgM
 IgG
 IgA
 IgD
 IgE
⚫ IgG, which is a bivalent antibody and constitutes
about 75 percent of the antibodies of the normal
person.

18.
Different Antibody structures

19.
Antibody
Isotype
Location
IgA
Found in mucosal areas, such as the gut,
respiratory tract and urogenital tract.
IgD
It has been shown to activate basophils and
mast cells to produce antimicrobial factors
IgE
Binds to allergens and triggers histamine
release from mast cells and basophils, and is
involved in allergy. Also protects against
parasitic worms
IgG
Provides the majority of antibody-based
immunity against invading pathogens.
The only antibody capable of crossing the
placenta to give passive immunity
IgM
Eliminates pathogens in the early stages of B
cell-mediated immunity before there is
sufficient IgG.

20.
Antibody class switching
⚫ Class switching is the process whereby an
activated B cell changes its antibody
production from IgM to either IgA, IgG, or IgE
depending on the functional requirements.
⚫ As antibody class is determined by the heavy
chain of the antibody, class switching is done
by replacing the heavy chain in the constant
region of the antibody and leaving the antigen
binding variable region as such.

21.
How class switching happens
⚫ This is done by a process called class switch
recombination and is an irreversible process.
⚫ A process occur whereby the constant region gene
is swapped from μ (IgM) to one of the other isotypes,
without altering the variable heavy chain gene
expression.

22.
What determines which class of
antibody is expressed?
⚫ CD4 T cells in the area produce different cytokines
and these cytokines interact with the B cells and
cause them to favour a particular antibody class.
For example, at mucosal surfaces, CD4 T cells will
often produce TGFβ which drives the B cells present
to produce IgG & IgA, whereas in allergy or during
parasite infection there is a large amount of IL-4
and IL-13 which skew towards IgE production.

23.
Mechanism of action of antibody
⚫ Antibodies act mainly in two ways to protect the
body against invading agents:
 (1) by direct attack on the invader and
 (2) by activation of the “complement system”
that then destroys the invader.

24.
Direct Action of Antibodies
⚫ The antibodies can inactivate the invading agent in
one of several ways, as follows:
1. Agglutination, in which antibodies "glue
together" foreign cells into clumps that are
attractive targets for phagocytosis
2. Precipitation, antigen (such as tetanus toxin)
and antibody becomes so large that it is
rendered insoluble and precipitates
3. Neutralization, in which the antibodies cover the
toxic sites of the antigenic agent
4. Lysis, antibodies are occasionally capable of
directly attacking membranes of cellular agents
and thereby cause rupture of the agent

25.
COMPLEMENT SYSTEM FOR
ANTIBODY ACTION
⚫ The complement system is a part of the immune
system that enhances (complements) the ability
of antibodies and phagocytic cells to
clear microbes and damaged cells from an organism
⚫ “Complement” is a collective term that describes a
system of about 30 proteins found in the blood,
⚫ synthesized by the liver, and normally circulating as
inactive precursors (pro-proteins).
⚫ The principal actors in this system are 11 proteins
designated C1 through C9, B, and D,

26.
Activation of complement system
⚫ Activated by binding of antigen & antibody
⚫ Followed by series of reactions ( Cascade)
⚫ Initial components acts as enzymes for the next step.
⚫ Two biochemical pathways activate the
complement system:
 the classical complement pathway,
 the alternative complement pathway,

27.
Classical complement pathway
⚫ The classical pathway is initiated by an antigen-
antibody reaction.
⚫ The antigen-antibody complex binds directly with
the C1 molecule of the complement system, setting
into motion a “cascade” of sequential reactions,

28.
The Classical complement pathway
C1 C1
C4 + C2 C4b2b + C4a
C3 C3b + C3a
C5 C5b + C5a
C6 + C7 C5b67
C8 + C9 C5b6789
Antigen –
antibody
complex

29.
The Alternate complement pathway
⚫ Also known as the Properdin Pathway
⚫ Part of innate immunity
⚫ Bypasses C1, C4, and C2
⚫ Does not require an antigen-antibody complex for
its activation.
⚫ Does not wait for antibody to be formed for
activation
⚫ Acts synergistically with the classical pathway
⚫ Usually activated by microorganisms and their
toxins. eg. bacteria, viruses, damaged tissue.

30.
The Alternate complement pathway
C3 C3b + C3a
C5 C5b + C5a
C6 + C7 C5b67
C8 + C9 C5b6789
C1 C1
C4 + C2 C42 + C4a
Antigen –
antibody
complex
Microorganism
(bacteria, virus etc)

31.
Effects of complement activation
1. Opsonization and phagocytosis. One of the products
of the complement cascade, C3b, strongly activates
phagocytosis by both neutrophils and macrophages,
causing these cells to engulf the bacteria to which
the antigen-antibody complexes are attached. This
process is called opsonization.
Opsonin
 A substance that promotes the phagocytosis of antigens
by binding to them.

32.
2. Lysis. One of the most important of all the
products of the complement cascade is the
lytic complex, C5b6789 known as Membrane
Attack Complex (MAC)
 This has a direct effect of rupturing the cell
membranes of bacteria or other invading
organisms.
 PNH
3. Neutralization of viruses. The complement
enzymes and other complement products can
attack the structures of some viruses and
thereby render them nonvirulent.

33.
4. Chemotaxis. Fragment C5a initiates chemotaxis
of neutrophils and macrophages, thus causing
large numbers of these phagocytes to migrate
into the tissue area adjacent to the antigenic
agent.
5. Activation of mast cells and basophils. Fragments
C3a, C4a, and C5a activate mast cells and
basophils, causing them to release histamine,
heparin, and several other substances into the
local fluids.
6. Inflammatory Effect

34.
C1 C1
C4 + C2 C42 + C4a
C3 C3b + C3a
C5 C5b + C5a
C6 + C7 C5b67
C8 + C9 C5b6789
(MAC)
Antigen –
antibody
complex
Opsonization of bacteria
Activate mast cell and basophil
Chemotaxis of WBC
Lysis of cells
Microorganism
(bacteria, virus etc)

35.
Scanning electron micrographs of E. coli showing (a) intact cells
and (c) cells killed by complement-mediated lysis.
Membrane Attack Complex
Attached to the bacterial cell
membrane

36.
Antigen presenting cells.
⚫ B lymphocyte, T lymphocytes respond to antigens
only when they are bound to surface of antigen-
presenting cells.
⚫ The three major types of antigen presenting cells
are macrophages, B lymphocytes, and dendritic
cells.
⚫ The dendritic cells, the most potent of the antigen-
presenting cells, are located throughout the body,
and their only known function is to present
antigens to T cells.

37.
⚫ specific molecules called MHC proteins (Major
histocompatibility Complex) are present on the
surface of antigen presenting cells which bind to
antigen.
⚫ There are two types of MHC proteins:
1. MHC I proteins, which present antigens to cytotoxic T
cells, and
2. MHC II proteins, which present antigens to T-helper cells.

38.
Activation of T cells requires interaction of T-cell receptors with an antigen that
is transported to the surface of the antigen-presenting cell by a major
histocompatibility complex (MHC) protein

39.
T- Lymphocyte
⚫ Lymphoid progenitor cells pre-processed in the
thymus gland, are called “T” lymphocytes to
designate the role of the thymus.
⚫ They are responsible for cell-mediated immunity.
⚫ there are thousands of different types of thymic
lymphocytes with specific reactivity against many
thousands of different antigens.

40.
⚫ The thymus makes certain that any T lymphocytes
leaving the thymus will not react against the body’s
own tissues.
⚫ About 98% of thymocytes die during the
development processes in the thymus by failing
either positive selection or negative selection

41.
Positive selection of ‘T’ Lymphocyte.
⚫ Positive selection "selects for" T cells capable of
interacting with MHC.
⚫ Thymocytes move deep into the thymic cortex,
where they are presented with self-antigens by
MHC.
⚫ Only those thymocytes that interact with MHC-I
or MHC-II appropriately (i.e., not too strongly or
too weakly) will receive a vital "survival signal".

42.
⚫ All that cannot (i.e., if they do not interact
strongly enough, or if they bind too strongly) will
die by "death by neglect" (no survival signal).
⚫ This process ensures that the selected T-cells will
have an MHC affinity that can serve useful
functions in the body
⚫ A thymocyte cells that interact well with MHC
class II molecules will eventually become CD4+ or
T helper cells,
⚫ A thymocytes that interact well with MHC class I
molecules mature into CD8+ or cytotoxic T cells.

43.
Negative selection of ‘T’ Lymphocyte.
⚫ Negative selection removes thymocytes that are
capable of strongly binding with "self" MHC
peptides.
⚫ Thymocytes that survive positive selection migrate
towards medulla in the thymus.
⚫ In the medulla, they are again presented with a
self-antigen presented on the MHC.
⚫ Thymocytes that interact too strongly with the self-
antigen receive an apoptotic signal that leads to
cell death.

44.
⚫ This process of negative selection is an important
component of central tolerance and serves to
prevent the formation of self-reactive T cells that
are capable of inducing autoimmune diseases in
the host.
⚫ Thus T cells that leave the thymus are self-
restricted, self-tolerant, and just around 3-4% of the
total thymocyte.

45.
Types of T Cells
⚫ T cells are classified into three major
groups:
1. T-helper cells,
2. Cytotoxic T cells, and
3. Suppressor T cells.

46.
T-Helper Cells
⚫ The most numerous of the T cells, usually
constituting more than three quarters of all of
them.
⚫ Help in the functions of the immune system, as
the major regulator of virtually all immune
functions.
⚫ Secrete protein mediators, called lymphokines,
that act on other cells of the immune system
and bone marrow cells.

47.
The most important lymphokines secreted
by the T-helper cells are:
⚫ Interleukin-2
⚫ Interleukin-3
⚫ Interleukin-4
⚫ Interleukin-5
⚫ Interleukin-6
⚫ Granulocyte-monocyte colony-stimulating
factor
⚫ Interferon-γ

48.
Functions of T-helper cells.
⚫ Stimulation of growth and proliferation of
Cytotoxic T Cells and Suppressor T Cells.
The lymphokine interleukin-2 has an especially
strong stimulatory effect in causing growth and
proliferation of both cytotoxic and suppressor T
cells
⚫ Stimulation of B-Cell growth and differentiation to
form Plasma cells and Antibodies.
Almost all the interleukins participate in the B-cell
response, especially interleukins 4, 5, and 6.

49.
⚫ Activation of the Macrophage System
Lymphokines cause chemotaxis and activate
the macrophages to cause far more efficient
phagocytosis, allowing them to attack and
destroy increasing numbers of pathogens.
⚫ Feedback Stimulatory Effect on the T-Helper
Cells
interleukin-2, have a direct positive feedback
effect in stimulating activation of the T-helper
cells thus amplifying the helper cell response

50.
⚫ It is the T-helper cells that are inactivated or
destroyed by the human immunodeficiency virus
(HIV).
⚫ This leaves the body almost totally unprotected
against infectious disease, therefore leading to
the now well known acquired immune deficiency
syndrome (AIDS).

51.
Cytotoxic T Cells
⚫ The cytotoxic T cell is a direct-attack cell
that is capable of killing microorganisms
and, at times, even some of the body’s own
cells.
⚫ these cells are called killer T cells.
⚫ The receptor proteins on the surfaces of the
cytotoxic cells cause them to bind tightly to
the antigenic cell and kill it.

52.
⚫ the cytotoxic T cell secretes hole-forming proteins,
called perforins, that literally punch round holes in the
membrane of the attacked cell.
⚫ the cytotoxic T cell releases cytotoxic substances
directly into the attacked cell.
⚫ Almost immediately, the attacked cell becomes
greatly swollen and lysis of the cell happens.

53.
Suppressor T Cells
⚫ They are capable of suppressing the functions of
both cytotoxic and T-helper cells.
⚫ the suppressor T-cell system plays an important
role in immune tolerance.
⚫ Since they regulate the function of other T cells
they are now known as Regulatory T cells

54.
Immunization
⚫ Acquired immunity can be actively generated by
the use of immunization / vaccination.
⚫ Immunization is also called active acquired immunity
or simply active immunity
⚫ Immunization has been used for many years to
produce acquired immunity against specific
diseases.
⚫ exposing a human, or an animal, to an immunogen
in a controlled way, so that the body can learn to
protect itself by mounting an appropriate immune
response

55.
⚫ Immunization can be done by:
1. Injecting dead organisms that are no longer
capable of causing disease but that still have some
of their chemical antigens. This type of immunization
is used to protect against typhoid fever, whooping
cough, diphtheria, and many other types of
bacterial diseases.
2. Injecting denatured toxins that have been treated
with chemicals so that their toxic nature has been
destroyed even though their antigens are still intact.
This procedure is used in immunizing against
tetanus, botulism, and other similar toxic diseases.

56.
3. Injecting live organisms that have been
“attenuated.”
This procedure is used to protect against
yellow fever, poliomyelitis, measles, and
many other viral diseases.

57.
Passive immunity
⚫ Temporary immunity can be achieved in a person
by injecting antibodies, activated T cells, or both
obtained from the blood of someone else or from
some other animal that has been actively
immunized against the antigen.
⚫ Such transfusion of antibodies or T lymphocytes to
confer immunity is called passive immunity.
⚫ Antibodies last in the body of the recipient for 2 to
3 weeks, and Activated T cells last from few hours
to few weeks

58.
Allergy And Hypersensitivity
⚫ An important undesirable side effect of immunity
⚫ an over-reaction of the immune system and these
reactions may be damaging and uncomfortable.
⚫ Hypersensitivity reactions can be classified into four
types.
 Type I: IgE mediated immediate reaction
 Type II: Antibody-mediated reaction (IgG or IgM
antibodies)
 Type III: Immune complex-mediated reaction
 Type IV: Cytotoxic, cell-mediated, delayed
hypersensitivity reaction

59.
ALLERGY CAUSED BY ACTIVATED T CELLS:
DELAYED-REACTION ALLERGY:
⚫ Delayed-reaction allergy is caused by
activated T cells and not by antibodies.
⚫ upon repeated exposure of antigen the
formation of activated helper and cytotoxic
T cells happens .
⚫ the eventual result of delayed reaction
allergies can be serious tissue damage.
⚫ The damage occurs in the tissue area
where the instigating antigen is present,

60.
“ATOPIC” ALLERGIES ASSOCIATED WITH EXCESS IgE
ANTIBODIES
⚫ Some people have an “allergic” tendency. Their
allergies are called atopic allergies because they
are caused by a nonordinary response of the
immune system.
⚫ The allergic tendency is characterized by the
presence of large quantities of IgE antibodies in
the blood.
⚫ These antibodies are called reagins or sensitizing
antibodies to distinguish them from the more
common IgG antibodies.

61.
⚫ A special characteristic of the IgE antibodies (the
reagins) is a strong propensity to attach to mast
cells and basophils.
⚫ Upon activation by a an allergen, IgE causes many
of the mast cells and basophils to rupture;
⚫ This releases chemicals like histamine, protease,
slow-reacting substance of anaphylaxis (which is a
mixture of toxic leukotrienes), eosinophil
chemotactic substance, neutrophil chemotactic
substance, heparin, and platelet activating factors.

62.
⚫ These substances cause such effects as:
 dilation of the local blood vessels;
 attraction of eosinophils and neutrophils
to the reactive site;
 increased permeability of the capillaries
withloss of fluid into the tissues; and
 contraction of local smooth muscle cells.